Using a Novel Microfabricated Model of the Alveolar-Capillary Barrier to Investigate the Effect of Matrix Structure on Atelectrauma.

The alveolar-capillary barrier is composed of epithelial and endothelial cells interacting across a fibrous extracelluar matrix (ECM). Although remodeling of the ECM occurs during several lung disorders, it is not known how fiber structure and mechanics influences cell injury during cyclic airway reopening as occurs during mechanical ventilation (atelectrauma). We have developed a novel in vitro platform that mimics the micro/nano-scale architecture of the alveolar microenvironment and have used this system to investigate how ECM microstructural properties influence epithelial cell injury during airway reopening. In addition to epithelial-endothelial interactions, our platform accounts for the fibrous topography of the basal membrane and allows for easy modulation of fiber size/diameter, density and stiffness. Results indicate that fiber stiffness and topography significantly influence epithelial/endothelial barrier function where increased fiber stiffness/density resulted in altered cytoskeletal structure, increased tight junction (TJ) formation and reduced barrier permeability. However, cells on rigid/dense fibers were also more susceptible to injury during airway reopening. These results indicate that changes in the mechanics and architecture of the lung microenvironment can significantly alter cell function and injury and demonstrate the importance of implementing in vitro models that more closely resemble the natural conditions of the lung microenvironment.

Sensitivity of conventional memory tests in multiple sclerosis: comparing the Rao Brief Repeatable Neuropsychological Battery and the Minimal Assessment of Cognitive Function in MS.

BACKGROUND: Cognitive impairment is common in multiple sclerosis (MS) affecting roughly 45-60% of patients. Because memory deficits have significant impact on employment, caregiver burden, and social functioning, neuropsychological (NP) assessment is often recommended. Two widely used and validated NP batteries for MS are the Rao Brief Repeatable Neuropsychological Battery (BRNB) and the Minimal Assessment of Cognitive Function in MS (MACFIMS). Although similar, these batteries differ in the specific auditory/verbal and visual/spatial memory tests employed. The relative sensitivity of these memory tests is unknown. METHODS: The BRNB and MACFIMS have considerable overlap but different memory tests: the former includes the Selective Reminding Test (SRT) and the 10/36 Spatial Recall Test (10/36) and the latter the California Verbal Learning Test, Second Edition (CVLT2) and Brief Visuospatial Memory Test, Revised (BVMTR). In 65 patients with MS and 46 demographically matched controls, we compared the sensitivity of these tests, and secondarily their respective batteries. RESULTS: The BRNB and MACFIMS were comparable in their overall sensitivity to disease status. Although the BVMTR showed greater discriminative validity than the 10/36, the CVLT2 and SRT were comparable in sensitivity. The SDMT was the most sensitive NP test across both batteries. CONCLUSIONS: We conclude that the BRNB and MACFIMS have comparable sensitivity among patients with MS. The sensitivity of the auditory/verbal memory tests from these batteries is similar, but the BVMTR appears to be more sensitive than the 10/36. Clinical implications are discussed.

Pseudophakia and polypseudophakia in the first year of life.

PURPOSE: To report a consecutive series of patients undergoing intraocular lens (IOL) implantation in the first year of life. A new procedure, referred to as temporary polypseudophakia, is reported. METHODS: A retrospective chart analysis was conducted. Ocular growth and refractive change, complications and reoperation rates, and outcomes were analyzed. RESULTS: Forty-seven eyes of 33 patients underwent IOL implantation in the first year of life. Average follow-up was 22 months (range, 7 weeks to 5 years). Thirty-two eyes of 22 patients had a single IOL implanted from 12 days to 11 months of age. Fifteen eyes of 11 infants received piggyback IOLs from 16 days to 6.8 months of age. Reoperation for complications within the anterior segment of the eye was needed in 23% of all patients (22% for single IOLs, 26% for piggyback IOLs). The average first postoperative refraction after single IOL was +7.98 D and after piggyback IOL was +1.67 D. The average last postoperative refraction was +1.76 D and -4.48 D, respectively. On average, eyes grew 2.68 mm over 17.5 months of follow-up. Eight patients were old enough for Snellen visual acuity, but each had deprivation amblyopia with visual acuities from 20/85 to 5/200. Of the remaining 25 patients, 17 had central, steady, and maintained fixation in the implanted eyes. CONCLUSION: IOL implantation in infancy is technically feasible and associated with a reoperation rate of approximately 25% in the first 2 years after implantation. Further follow-up is required before meaningful visual acuity data and long-term results can be reported.

Using clinical practice analysis to improve care.

BACKGROUND: Improving clinical outcomes requires that physicians examine and change their clinical practice. Sustaining outcome improvements requires a dedicated and dynamic program of analyzing and improving patient care. In 1992 North Mississippi Health Services (NMHS) implemented a program to improve physicians' clinical efficiency. CLINICAL PRACTICE ANALYSIS ( CPA): CPA uses evidenced-based guidelines and examines each physician's resource utilization, processes, and outcomes for a diagnosis or procedure. Clinical practice profiles are developed, and individual performance is compared to local and national benchmarks and presented to physicians. The CPA process is used on its own or as a component of more comprehensive performance improvements projects. Physicians have been engaged in outcome improvement by more than 55 CPA projects. RESULTS: NHMS has progressively reduced its Medicare loss and its length of stay (LOS) to 4.9 days. Mortality and readmission rates have been reduced in specific diagnoses. The community-acquired pneumonia project reduced the LOS from 7.7 to 5.1 days, decreaesed the mortality rate from 8.9% to 5.0%, and decreased the cost of care from $4,269 to $3,834. The ischemic stroke project reduced the aspiration pneumonia rate from 6.4% to 0% and mortality from 11.0% to 4.6%. Patients' average LOS decreased from 10.7 days to 6.5 days, and their cost of care was reduced by $1,100 per patient. DISCUSSION: Providing individualized data has engaged physicians in improving outcomes. The program has evolved from improving efficiency to managing outcomes and from simple CPA projects to integrated performance improvement projects; however, the CPA process remains the cornerstone of the current process.

The effect of anemia on retinopathy of prematurity in extremely low birth weight infants.

OBJECTIVE: Numerous risk factors for development of retinopathy of prematurity (ROP) in very low birth weight infants have been identified in the literature. However, the role of anemia in the development of ROP has not been adequately addressed. STUDY DESIGN: We retrospectively examined the medical records of all infants weighing < or = 800 g who were admitted to a university hospital between July 1, 1992 and December 30, 1997. Highest and lowest hemoglobin and hematocrit values and the number of blood transfusions were recorded at each week of life during hospitalization. Gestational age at birth, birth weight, race, sex, oxygen status, history of bronchopulmonary dysplasia, length of hospital stay, and sepsis were also identified as potential risk factors. Data were analyzed using logistic regression to adjust for these confounding variables. RESULTS: Infants were grouped according to ROP status in the following manner: stage 0 to 1 ROP, stage 2 ROP, and stage 3 to threshold ROP. Sex, gestational age at birth, bronchopulmonary dysplasia, ventilator days, length of hospital stay, and number of blood transfusions were significantly associated with severity of ROP by univariate analysis. Using a logistic regression model, only gestational age (p = 0.007) and number of blood transfusions (p = 0.04) remained statistically significant. CONCLUSIONS: Anemia did not affect severity of ROP as an independent risk factor. However, the number of blood transfusions did affect the highest stage of ROP in this group of premature infants. Infants who remained severely anemic (Hgb < or = 8 g/dl or Hct < or = 25%) for longer periods of time developed milder ROP than less anemic infants.

Effects of hospitalists on cost, outcomes, and patient satisfaction in a rural health system.

PURPOSE: Previous studies have examined the effects of hospitalists in urban academic hospitals. We compared the outcomes of patients treated by hospitalists with those of patients treated by internists at a 647-bed rural community hospital. SUBJECTS AND METHODS: The 443 patients in the hospitalists' 10 most common diagnosis-related groups (DRGs) were compared with 1,681 patients in the same DRGs who were cared for by internists in fiscal year 1998. Length of stay, cost of care, patient illness severity, patient satisfaction, 30-day readmission rate, inpatient mortality, discharge status, and resource utilization were compared. RESULTS: The hospitalists' patients had a shorter mean (+/- SD) length of stay (4.1 +/- 3.0 days versus 5.5 +/- 4.9 days, P <0.001) and their cost of care was less than that of the internists' patients ($4,098 +/- $2,455 versus $4,658 +/- $4,084, P <0.001). Analyses that adjusted for patient age, race, sex, insurance status, severity of illness, and specific medical comorbidities confirmed these differences. The differences between hospitalists and internists were most apparent among very ill patients. Mortality rates were similar (4.5% for hospitalists versus 4.9% for internists, P = 0.80), as were the readmission rates (4.5% for hospitalists versus 5.6% for internists, P = 0.41). Patient satisfaction was similar for both groups. The internists used more resources in 8 of 11 categories. CONCLUSIONS: The hospitalists provided cost-effective care, particularly for the sickest patients, with good outcomes and patient satisfaction.

Postoperative intraocular pressure elevation after the use of Healon GV in pediatric cataract surgery.

Intraocular pressure elevation after the use of viscoelastic agents in uncomplicated cataract surgery has been well documented in adults. However, pediatric patients are thought to clear residual viscoelastic agents from the anterior chamber more easily than adults, presumably because of healthier trabecular meshwork. (1) We report on a series of 4 eyes of 4 children with previously normal intraocular pressure who underwent cataract extraction with primary (3 patients) or secondary (1 patient) intraocular lens implantation with Healon GV, which was complicated by marked postoperative intraocular pressure elevation (greater than 30 mm Hg). The patients, aged 5 to 14 years, had an intraocular pressure ranging from 34 to 50 mm Hg with Tonopen or applanation tonometry 1 day, postoperatively associated with nausea, eye pain, and microcystic corneal edema. Viscoelastic material was not entirely removed during surgery. Each of these cases occurred after a change in our preferred viscoelastic agent from one with less viscosity to Healon GV. Medical management controlled the elevated intraocular pressure in all cases without affecting the visual outcome. However, 1 patient with intractable nausea and vomiting required hospitalization for rehydration. With meticulous removal of all viscoelastic material at the completion of surgery, we have not documented any additional cases of postoperative pressure elevation.

In-the-bag secondary intraocular lens implantation in children.

BACKGROUND: Surgery for congenital cataracts in early infancy usually includes a primary posterior capsulectomy and an anterior vitrectomy. Initially, most of these infants have aphakia after surgery. Over time, remaining equatorial lens epithelial cells produce new cortical fibers, resulting in a ring of cortex trapped between the lens equator and the fused anterior and posterior capsulectomy edges. A potential space is maintained between the anterior and posterior capsular leaflets. We describe a technique for placing a secondary intraocular lens (IOL) within the capsular bag. PATIENTS AND METHODS: Eight children, ranging in age from 11 months to 14 years, who originally had aphakia after cataract extraction were operated on with the intent to reopen the capsular bag and place an IOL in the bag. RESULTS: Secondary in-the-bag IOL implantation was successfully completed in 7 of 8 children. This was accomplished by reopening the capsular bag 360 degrees at the edge of the fused anterior and posterior capsulectomy remnants, using the previously published vitrectorhexis technique. Residual cortical material was aspirated, and an IOL was placed within the capsular bag. In 1 child, aged 14 years, the capsular bag was reopened, but the lens was placed in the ciliary sulcus because the new anterior capsule edge could not be visualized for 360 degrees . CONCLUSION: Placement of secondary IOLs within the capsular bag can be accomplished successfully for selected patients in the pediatric population. Surgeons operating on infantile cataracts without primary IOL placement can facilitate capsular IOL sequestration later by limiting the anterior and posterior capsulectomy to 4 to 5 mm and performing a generous anterior vitrectomy to help prevent secondary closure of the smaller capsulectomy.

A rapid method to separate endosomes from lysosomal contents using differential centrifugation and hypotonic lysis of lysosomes.

Here we describe a fast and efficient subcellular fractionation procedure that permits lysosomes to be separated from endosomes. Differential centrifugation is used to isolate a subcellular fraction containing both endosomes and lysosomes. Because lysosomes are sensitive to osmotic stress, hypotonic conditions destroy them, whereas endosomes, which are osmotically insensitive, stay intact. We demonstrate that hypotonic lysis of an endosome-lysosome-pool releases 85% of the lysosomes into the supernatant as measured by the activity of the lysosomal marker enzyme N-acetyl-beta-D-glucosaminidase (beta-AGA). The endosomal fraction is thoroughly characterised using a variety of subcellular markers. After pulsing cells with fluorescein isothiocyanate labelled transferrin (FITC-Tf), only about 12% of the marker is released under hypotonic conditions. A typical fractionation procedure takes about 1-2 h from initial cell homogenisation. The fractionation gives a pure lysosomal fraction (fraction L) containing high activities of lysosomal enzymes and an endosomal fraction (fraction E) reflecting different stages of endosomes.

The quality of medical evidence in hematology-oncology.

PURPOSE: The purpose of this study was to evaluate the quality of the medical evidence available to the clinician in the practice of hematology/oncology. METHODS: We selected 14 neoplastic hematologic disorders and identified 154 clinically important patient management decision/interventions, ranging from initial treatment decisions to those made for the treatment of recurrent or refractory disease. We also performed a search of the scientific literature for the years 1966 through 1996 to identify all randomized controlled trials in hematology/oncology. RESULTS: We identified 783 randomized controlled trials (level 1 evidence) pertaining to 37 (24%) of the decision/interventions. An additional 32 (21%) of the decision/interventions were supported by evidence from single arm prospective studies (level 2 evidence). However, only retrospective or anecdotal evidence (level 3 evidence) was available to support 55% of the identified decision/interventions. In a retrospective review of the decision/interventions made in the management of 255 consecutive patients, 78% of the initial decision/interventions in the management of newly diagnosed hematologic/oncologic disorders could have been based on level 1 evidence. However, more than half (52%) of all the decision/interventions made in the management of these 255 patients were supported only by level 2 or 3 evidence. CONCLUSIONS: We conclude that level 1 evidence to support the development of practice guidelines is available primarily for initial decision/interventions of newly diagnosed diseases. Level 1 evidence to develop guidelines for the management of relapsed or refractory malignant diseases is currently lacking.

The Ahmed valve in refractory pediatric glaucoma.

PURPOSE: To evaluate the efficacy of the Ahmed Glaucoma Valve implant in pediatric patients with refractory glaucoma. METHODS: A retrospective chart review was conducted of 27 eyes from 23 consecutive pediatric patients (younger than 18 years) with refractory glaucoma treated with Ahmed Glaucoma Valve implant placement. The main outcome measure was time after surgery without failure. Success was defined as an intraocular pressure of 21 mm Hg or less without visually devastating complications or additional glaucoma surgery (exclusive of tube revision). Previous cycloablation, which was present in a subset of eyes, was examined as a possible influence on postoperative intraocular pressure control, glaucoma medication dependence, and surgical success. RESULTS: The median patient age was 4.8 years (range, 0.3 to 16.8 years), with a follow-up of 3 to 31 months (mean, 12.6 +/- 8.2 months). Intraocular pressure was reduced from a preoperative mean of 32.8 +/- 7.5 mm Hg to 16.7 +/- 5.4 mm Hg at 18 months postoperatively, with an overall success rate of 85.2% at last follow-up. Cumulative probabilities of success by Kaplan-Meier analysis were 90.6% at 12 months and 58.3% at 24 months. Compared with those that did not undergo previous cycloablation, eyes that had undergone previous cycloablation had a lower mean postoperative intraocular pressure at 3- and 6-month follow-up (P < .001 and P = .057, respectively) and required fewer glaucoma medications at postoperative examination time points up to 18 months (P < or = .01 at each time point). Fifteen eyes (56%) required glaucoma medications after surgery. The most common complication was corneal-tube contact, which occurred in five eyes (18.5%). One eye with a wound leak required anterior chamber reformation. Retinal detachment occurred in one aphakic eye 2 years postoperatively, resulting in loss of vision. One eye with neovascular glaucoma required enucleation after an enlarging (presumably preexisting) medulloepithelioma was discovered. CONCLUSIONS: Ahmed Glaucoma Valve implantation is a useful therapy for the treatment of refractory pediatric glaucoma, and it may be safely used in a subgroup of eyes with uncontrolled intraocular pressure despite previous cycloablation procedures.

Clinical efficiency tools improve stroke management in a rural southern health system.

BACKGROUND AND PURPOSE: Ischemic stroke is a high-volume and financially draining diagnosis at this rural health system. The purpose of this clinical practice analysis was to identify resource utilization and clinical process inefficiencies and to promote clinically efficient, evidence-based improvements. METHODS: A retrospective analysis of medical record and financial databases of 356 patients with ischemic stroke was performed. The medical record data were adjusted for severity, and outliers were eliminated. The resources utilized by each physician were determined. Comparative graphs were prepared, presented, and discussed. The physicians implemented two types of changes: (1) alteration of resource utilization and consultation patterns and (2) support of clinical process improvement. In 1997, a follow-up analysis of 399 patients was performed. RESULTS: The initial comparison of internists' to neurologists' patient populations found the following: patient age (75 versus 65 years), patient severity ratings (2.8 versus 2.5), length of stay (10.7 versus 8.8 days), costs ($7360 versus $6862), mortality rates (12.5% versus 8.9%), and aspiration pneumonia rate (8.5% versus 3.8%). A comparison of the 1995 analysis to the 1997 analysis revealed the following per patient resource utilization decreases (all P < 0.05): chemistry laboratory, 2.65 to 1.95 studies; intravenous fluids, 2.85 to 1.85 L; oxygen use, 6.06 to 2.75 U; and nifedipine use, 1.62 to 0.33 capsules. The clinical process improvements resulted in the following overall outcomes (all P < 0.05 except mortality): length of stay (7.2 days), nonadjusted costs ($6246), mortality (6.5%), and rates of pneumonia (2.7%). CONCLUSIONS: Objective analysis of resource utilization resulted in physicians changing their individual management of stroke and collectively supporting clinical process changes that improved clinical and financial outcomes.

Clinical applications of computer-based health information.

Competitive health care systems are improving their clinical and cost efficiency by performing clinical practice analyses. Large numbers of severity-adjusted cases provide the most objective data for making clinical efficiency decisions. The most cost-effective way to perform these analyses is to utilize well-coded, computer-based health information. This requires consistent coding of patients' comorbidities and complications as well as an interactive working relationship between coders and clinicians providing the clinical practice analysis. The article describes one hospital's evolving clinical efficiency information needs, how its health information system met them, the clinical practice analysis procedure, and the outcomes of this clinical practice analysis.

Argon vs diode laser trabeculoplasty.

PURPOSE: To compare the efficacy of diode laser and argon laser trabeculoplasty in a randomized prospective study of 11 paired fellow eyes. METHODS: Fellow eyes of 11 patients, having had no prior laser trabeculoplasty and requiring laser trabeculoplasty to lower intraocular pressure, were randomly assigned prospectively to diode laser trabeculoplasty in one eye and argon laser trabeculoplasty in the other eye. RESULTS: In the diode laser group, the average baseline intraocular pressure was 21.6 +/- 2.0 mm Hg before trabeculoplasty and 19.6 +/- 2.1 mm Hg (or a 7.7% +/- 11.5% mean pressure reduction) at 1 month, 19.3 +/- 2.6 mm Hg (or a 6.9% +/- 13.5% mean reduction) at 2 months, and 19.0 +/- 3.3 mm Hg (or a 2.4% +/- 16.9% mean reduction) at 3 months postoperatively. In the argon laser group, the average intraocular pressure was 24.4 +/- 3.5 mm Hg before treatment and 17.6 +/- 1.7 mm Hg (or a 24.7% +/- 11.4% mean pressure reduction) at 1 month, 16.8 +/- 2.5 mm Hg (or a 26.7% +/- 15.3% mean reduction) at 2 months, and 15.5 +/- 1.2 mm Hg (or a 30.0% +/- 16.5% mean reduction) at 3 months after laser trabeculoplasty. The difference between argon and diode laser intraocular pressure reduction was statistically significant at 1 month (P < .01), 2 months (P < .01), and 3 months (P < .05) after treatment. CONCLUSION: Argon laser trabeculoplasty appears to be more effective than diode laser therapy in lowering intraocular pressure during the first 3 months after treatment.

Triterpenoid saponins from Mimosa pigra.

Two novel triterpene glycosides have been isolated from Mimosa pigra. The aglycone of these two compounds was identified as machaerinic acid by 1H- and 13C-nmr spectroscopy and by comparison with an authentic sample. This aglycone is substituted at position C-3 by an identical oligosaccharide chain in these glycosides, and at position C-21 by either a Z/E-methoxycinnamic [1] unit or an E-cinnamic acid [2] unit.

Implications of the concepts "coping" and "quality of life" for criteria of course and outcome.

The Berlin Coping Study is a prospective longitudinal project with schizophrenic patients investigating the relationship between coping strategies and course and outcome. We find that some psychological issues relevant for both clinical practice and psychiatric research, and especially for pharmacological therapy, have been rather neglected up to now. The investigation of coping strategies leads to accentuating the patients' subjective individual views concerning their demands, goals, and coping activities in daily living and their schizophrenic illness. The concept of quality of life is increasingly receiving attention in various domains of professional care and it is very relevant to the issues discussed here. Consequences of this approach for therapy and research are outlined.

Physiological and Environmental Requirements for Poplar (Populus deltoides) Bark Storage Protein Degradation.

In poplar (Populus deltoides Bartr. ex Marsh), a 32-kD bark storage protein (BSP) accumulates in the bark during autumn and winter and declines during spring shoot growth. We investigated the physiological and environmental factors necessary for the degradation of poplar BSP. Poplar plants were exposed to short-day (SD) photoperiods for either 28 or 49 d. Plants exposed to short days for 28 d formed a terminal bud but were not dormant, whereas exposure to short days for 49 d induced bud dormancy. BSP accumulated in bark of plants exposed to both SD treatments. The level of BSP declined rapidly when nondormant plants were returned to long days. BSP levels did not decline in dormant plants that were exposed to long-day (LD) conditions. If dormant plants were first treated with either low temperatures (0[deg]C for 28 d) or with 0.5 M H2CN2 to overcome dormancy and then returned to long days, the level of BSP declined. Removal of buds from non-dormant or dormant plants in which dormancy had been overcome inhibited the degradation of BSP in LD conditions. BSP mRNA levels rapidly declined in plants exposed to long days, irrespective of the dormancy status of the plants or the presence or absence of buds. These results indicate that the buds of poplars are somehow able to communicate with bark storage sites and regulate poplar BSP degradation. These results further support an association of BSP mRNA levels with photoperiod because short days stimulate BSP mRNA accumulation, whereas long days result in a decline of BSP mRNA abundance.

Diuretic action of aqueous Orthosiphon extract in rats.

An aqueous extract of Orthosiphonis folium, given orally, enhances considerably ion excretion in rat to a level comparable to that obtained with furosemide. No aqueretic action is observed. The increased ion excretion is not due to the potassium content of the starting material.